1-[bis[3-(dimethylamino)propyl]amino]propan-2-ol

Biodegradation in water and sediment: simulation tests

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

biodegradation in water: simulation testing on ultimate degradation in surface water

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

In order to identify the relevant degradation products of1-[bis[3-(dimethylamino)propyl]amino]propan-2-ol (CAS n. 67151-63-7) as a standard information requirement according to Column 1, Section 9.2.3 of Annex IX to REACH and for assessment of potential PBT/vPvB properties, degradation products were predicted using the EAWAG-BBD Pathway Prediction System.
1. SOFTWARE
EAWAG-BBD Pathway Prediction System (http://eawag-bbd.ethz.ch/predict/)
2. MODEL (incl. version number)
EAWAG-BBD Pathway Prediction System: Last updated January 18, 2016.
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See attached QPRF
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
The EAWAG-BBD Pathway Prediction System predicts (EAWAG-BBD PPS) microbial catabolic reactions using substructure searching, a rule-base, and atom-to-atom mapping. The system is able to recognize organic functional groups found in a compound and predict transformations based on biotransformation rules. The biotransformation rules are based on reactions found in the EAWAGBBD
database or in the scientific literature. The EAWAG-BBD database contains information on microbial biocatalytic reactions and biodegradation pathways for primarily xenobiotic, chemical compounds. Individual reactions and metabolic pathways are presented with information on the starting and intermediate chemical compounds, the organisms that transform the compounds, the enzymes, and the genes. The EAWAG-BBD (Biocatalysis/Biodegradation Database) is a manually curated database containing information on over 1350 microbial catabolic reactions and about 200 biodegradation pathways. The EAWAG-PPS (Pathway Prediction System) predicts biodegradation pathways using 250 biotransformation rules based on data in the BBD (Biocatalysis/Biodegradation Database) and the scientific literature. Further details can be found in the attached QMRF.
5. APPLICABILITY DOMAIN
Although there is no specifically identified applicability domain for EAWAG-BBD PPS, there are certain chemicals whose biodegradation profile should not be predicted with the system. There are a number of chemical classes that should not be investigated using the current version of the Pathway Prediction System (PPS). Compounds modelled with the EAWAG-BBD PPS can be structurally compared to the compounds present in the EAWAG-BBD database, which presently contains 1400 compounds.
The experimental biotransformation data on which the biotransformation rules within the model are based, originate from data on these 1400 substances. More information on the model's applicability domain can be found in the attached QMRF and QPRF.
6. ADEQUACY OF THE RESULT
The results are considered appropriate to fulfil the REACH requirements for identification of degradation products (Annex IX, Section 9.2.3.). The compounds meet the criteria for applicability of the EAWAG-BBD model. None of the constituents fall within the categories of chemicals that should not be investigated with the model. More information on this can be found in the attached QPRF.

Principles of method if other than guideline:

- Software tool(s) used including version: EAWAG-BBD (last update: January 2016)
- Model(s) used: EAWAG-BBD Pathway Prediction System
- Model description: see field 'Justification for non-standard information', see attached QMRF
- Justification of QSAR prediction: see field 'Justification for type of information', see attached QPRF

GLP compliance:

no

Oxygen conditions:

aerobic

Inoculum or test system:

other: model calculation

Details on source and properties of surface water:

The model makes predictions for chemicals exposed to air, moist soil or water at moderate temperature and pH

Parameter followed for biodegradation estimation:

other: The model makes predictions for chemicals exposed to air, moist soil or water at moderate temperature and pH

Details on study design:

For the purpose of this QSAR analysis, only products formed through "Very likely" and "Likely" reactions were included.

Key result

Remarks on result:

other: formation of 39 transformation products via aerobic degradation was predicted; 21 transformation products were predicted to be not readily biodegradable, 18 were predicted to be readily biodegradable.

Transformation products:

not specified

The EAWAG-BBD PPS system predicted that the metabolites in the table below would be likely or very likely formed by aerobic microbial degradation.

#	Name	CAS number (EC number)	Smiles
1	N,N-Dimethyl-N'-[3-(methylamino)propyl]-1,3-propanediamine	-	CNCCCNCCCN(C)C
2	Lactaldehyde	598-35-6	CC(O)C=O
3	lactate anion	113-21-3	CC(O)C([O-])=O
4	1-{[3-(Dimethylamino)propyl]amino}-2-propanol	77463-83-3	CC(O)CNCCCN(C)C
5	1-{[3-(Dimethylamino)propyl]amino}acetone	-	CN(C)CCCNCC(C)=O
6	3-(Dimethylamino)propanal	70058-23-0	CN(C)CCC=O
7	N,N-Dimethyl-β-alanine	6300-04-5	CN(C)CCC([O-])=O
8	3-(dimethylamino)-1-propylamine	109-55-7 (203-680-9)	CN(C)CCCN
9	(±)-1-Amino-2-propanol	78-96-6 (201-162-7)	CC(O)CN
10	3-(Methylamino)propanal	79036-83-2	CNCCC=O
11	Methylglyoxal	78-98-8 (201-164-8)	CC(=O)C=O
12	DMAPAPA	10563-29-8 (234-148-4)	CN(C)CCCNCCCN
13	N-Methyl-N'-[3-(methylamino)propyl]-1,3-propanediamine	75403-53-1	CNCCCNCCCNC
14	N-(3-Aminopropyl)-N'-methyl-1,3-propanediamine	16968-18-6 (241-042-1)	CNCCCNCCCN
15	(2E)-3-(Methylamino)acrylonitrile	74300-87-1	CNCCCN
16	3-Aminopropanal	352-92-1	NCCC=O
17	3-(Methylamino)propanoate	-	CNCCC([O-])=O
18	bis(3-aminopropyl)amine	56-18-8 (200-261-2)	NCCCNCCCN
19	1,3-Diaminopropane	109-76-2 (203-702-7)	NCCCN
20	3-Aminopropanoate	23297-31-6	NCCC([O-])=O
21	(2E)-3-[(3-Hydroxypropyl)amino]acrylic acid	-	[O-]C(=O)CCNCCC=O
22	3,3'-Iminodipropanoic acid	505-47-5 (208-009-3)	[O-]C(=O)CCNCCC([O-])=O
23	(2E)-3-[(2-Hydroxypropyl)amino]acrylic acid	-	CC(=O)CNCCC([O-])=O
24	aminoacetone	298-08-8 (201-182-6)	CC(=O)CN
25	pyruvate	57-60-3	CC(=O)C([O-])=O
26	1-[(3-Aminopropyl)amino]-2-propanol	-	CC(O)CNCCCN
27	1-[3-(dimethylamino)propyl-[3-(methylamino)propyl]amino]propan-2-ol	-	CNCCCN(CCCN(C)C)CC(C)O
28	1-[bis[3-(dimethylamino)propyl]amino]propan-2-one	-	CN(C)CCCN(CCCN(C)C)CC(C)=O
29	~{N}-[3-(dimethylamino)propyl]-~{N}',~{N}'-dimethyl-propane-1,3-diamine	-	CN(C)CCCNCCCN(C)C
30	3-[3-(dimethylamino)propylamino]propanal	-	CN(C)CCCNCCC=O
31	1-[3-(methylamino)propylamino]propan-2-ol	-	CNCCCNCC(C)O
32	1-[3-aminopropyl-[3-(dimethylamino)propyl]amino]propan-2-ol	-	CC(O)CN(CCCN)CCCN(C)C
33	1-[3-(dimethylamino)propyl-[3-(methylamino)propyl]amino]propan-2-one	-	CNCCCN(CCCN(C)C)CC(C)=O
34	1-[3-(methylamino)propylamino]propan-2-one	-	CNCCCNCC(C)=O
35	1-(3-aminopropylamino)propan-2-one	-	CC(=O)CNCCCN
36	1-[3-aminopropyl-[3-(dimethylamino)propyl]amino]propan-2-one	-	CN(C)CCCN(CCCN)CC(C)=O
37	1-[bis[3-(methylamino)propyl]amino]propan-2-one	-	CNCCCN(CCCNC)CC(C)=O
38	1-[3-aminopropyl-[3-(methylamino)propyl]amino]propan-2-one	-	CNCCCN(CCCN)CC(C)=O
39	1-[bis(3-aminopropyl)amino]propan-2-one	-	CC(=O)CN(CCCN)CCCN

Conclusions:

Degradation (end) products of 1-[bis[3-(dimethylamino)propyl]amino]propan-2-ol were identified by use of QSAR.
The EAWAG-BBD Pathway Prediction System identified 39 metabolites for 1-[bis[3-(dimethylamino)propyl]amino]propan-2-ol (CAS n. 67151-63-7) likely or very likely to be formed by microbial degradation under aerobic conditions

Executive summary:

In order to identify the relevant degradation products of 1-[bis[3-(dimethylamino)propyl]amino]propan-2-ol (CAS n. 67151-63-7) as a standard information requirement according to Column 1, Section 9.2.3 of Annex IX to REACH and for assessment of potential PBT/vPvB properties, degradation products were predicted using the EAWAG-BBD Pathway Prediction System. The PBT/vPvB assessments of 1-[bis[3-(dimethylamino)propyl]amino]propan-2-ol as well as the predicted (end) degradation products were determined and are included in report "ZR50_biodeg_products_PBT_Assessment.pdf".
QMRF and QPRF documentation has been included to support the QSAR modelling results.

Reference 2

Endpoint:

biodegradation in water: sediment simulation testing

Data waiving:

exposure considerations

Justification for data waiving:

the study does not need to be conducted because direct and indirect exposure of sediment is unlikely

Transformation products:

no

Description of key information

A QSAR exercise was completed for endpoint coverage. The relevant degradation products of the substance were identified by means of EAWAG-BBD Pathway Prediction System model. 39 degradation products were identified, and these were then assessed for their P (B and T) properties in view of the PBT/vPvB assessment.
The biodegradability of each of the degradation products was predicted using the QSAR model BIOWIN available in the EPI Suite software. Of the 39 degradation products, 21 were predicted to be not readily biodegradable. The remaining 18 degradation products were predicted to be readily biodegradable.